GENESIS 1.1: A hybrid‐parallel molecular dynamics simulator with enhanced sampling algorithms on multiple computational platforms

Kobayashi, Chigusa; Jung, Jaewoon; Matsunaga, Yasuhiro; Mori, Takaharu; Ando, Tadashi; Tamura, Koichi; Kamiya, Motoshi; Sugita, Yuji

doi:10.1002/jcc.24874

Cited by 168 publications

(159 citation statements)

References 118 publications

(311 reference statements)

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“…All MD simulations were performed with the development version of GENESIS. 43,44 The force field parameter set for water molecules was TIP3P, 45,46 and those for protein and lipids were CHARMM36. 47,48 We used revised parameters for ATP 49 and magnesium ions.…”

Section: Methodsmentioning

confidence: 99%

Chemo-mechanical Coupling in the Transport Cycle of a Type II ABC Transporter

Tamura

Sugimoto

Shiro

et al. 2018

Preprint

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28 29 ATP-binding cassette (ABC) transporters are integral membrane proteins that 30 translocate a wide range of substrates across biological membranes, harnessing free 31 energy from the binding and hydrolysis of ATP. To understand the mechanism of the 32 inward-to outward-facing transition that could be achieved by tight regulation of 33 ATPase activity through extensive conformational changes of the protein, we applied 34 template-based iterative all-atom molecular dynamics (MD) simulation to the heme 35 ABC transporter BhuUV-T. The simulations, together with biased MDs, predict two 36 new conformations of the protein, namely, occluded (Occ) and outward-facing (OF) 37 conformations. The comparison between the inward-facing crystal structure and the 38 predicted two structures shows atomic details of the gating motions at the 39 transmembrane helices and dimerization of the nucleotide-binding domains (NBDs). 40 The MD simulations further reveal a novel role of the ABC signature motifs 41 (LSGG[Q/E]) at the NBDs in decelerating ATPase activity in the Occ form through 42 sporadic flipping of the side chains of the LSGG[Q/E] catalytic serine residues. The 43 orientational changes are coupled to loose NBD dimerization in the Occ state, whereas 44 they are blocked in the OF form where the NBDs are tightly dimerized. The 45 chemo-mechanical coupling mechanism may apply to other types of ABC transporters 46 having the conserved LSGG[Q/E] signature motifs. 47Occ state and closure of the cytoplasmic gate are thought to result from the binding of 129 ATP and dimerization of the NBDs (BhuVs) (Figure 1c). The question which then arises 130 is: how is the hydrolysis of ATP prevented in the Occ state, such that futile cycling back 131 to the IF state is avoided, before formation of the OF state? To solve this problem, we 132 analyzed MD trajectories of BhuUV-T starting from predicted Occ and OF 133 conformations and arrived at a novel chemo-mechanical coupling mechanism that 134 regulates ATPase activity by way of reorientation of the serine residues of the 135 LSGG[Q/E] motifs in type II ABC transporters. The proposed mechanism likely 136

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Section: Methodsmentioning

confidence: 99%

Chemo-mechanical Coupling in the Transport Cycle of a Type II ABC Transporter

Tamura

Sugimoto

Shiro

et al. 2018

Preprint

Self Cite

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“…We pushed forward and tried simulations on STMV and Such a setup was chosen in order to provide reference numbers, but the future performances can likely be accelerated substantially. At present, we need much more cores to get results comparable to those of other prominent codes [27][28][29][30]. Nevertheless, we decided to make performances measurements, firstly to get an idea of the boost that vectorization can provide in this case and, secondly, to know if we can still benefit from the scalability of the code, which is one of its greatest strengths.…”

Section: Sequential Performancementioning

confidence: 99%

Raising the Performance of the Tinker-HP Molecular Modeling Package [Article v1.0]

Jolly

Durán

Lagardère³

et al. 2019

LiveCoMS

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This living paper reviews the present High Performance Computing (HPC) capabilities of the Tinker-HP molecular modeling package. We focus here on the reference, double precision, massively parallel molecular dynamics engine present in Tinker-HP and dedicated to perform large scale simulations. We show how it can be adapted to recent Intel ® Central Processing Unit (CPU) petascale architectures. First, we discuss the new set of Intel ® Advanced Vector Extensions 512 (Intel AVX-512) instructions present in recent Intel processors (e.g., the Intel ® Xeon ® Scalable and Intel ® Xeon Phi ™ 2nd generation processors) allowing for larger vectorization enhancements. These instructions constitute the central source of potential computational gains when using the latest processors, justifying important vectorization efforts for developers. We then briefly review the organization of the Tinker-HP code and identify the computational hotspots which require Intel AVX-512 optimization and we propose a general and optimal strategy to vectorize those particular parts of the code. We present our optimization strategy in a pedagogical way so it can benefit other researchers interested in improving performances of their own software. Finally we compare the performance enhancements obtained to unoptimized code, both sequentially and at the scaling limit in parallel for classical non-polarizable (CHARMM) and polarizable force fields (AMOEBA).

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“…We have developed the GENESIS MD software to overcome current size limitations of MD. [19,20] The new domain decomposition scheme in GENESIS produces highly efficient parallelization in real-space calculation, enabling simulations of very large systems. [21] Efficient FFT parallelization schemes have been developed in GENESIS for high performance on the K computer.…”

Section: Introductionmentioning

confidence: 99%

Scaling molecular dynamics beyond 100,000 processor cores for large‐scale biophysical simulations

et al. 2019

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The growing interest in the complexity of biological interactions is continuously driving the need to increase system size in biophysical simulations, requiring not only powerful and advanced hardware but adaptable software that can accommodate a large number of atoms interacting through complex forcefields. To address this, we developed and implemented strategies in the GENESIS molecular dynamics package designed for large numbers of processors. Long-range electrostatic interactions were parallelized by minimizing the number of processes involved in communication. A novel algorithm was implemented for nonbonded interactions to increase single instruction multiple data (SIMD) performance, reducing memory usage for ultra large systems.Memory usage for neighbor searches in real-space nonbonded interactions was reduced by approximately 80%, leading to significant speedup. Using experimental data describing physical 3D chromatin interactions, we constructed the first atomistic model of an entire gene locus (GATA4). Taken together, these developments enabled the first billion-atom simulation of an intact biomolecular complex, achieving scaling to 65,000 processes (130,000 processor cores) with

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GENESIS 1.1: A hybrid‐parallel molecular dynamics simulator with enhanced sampling algorithms on multiple computational platforms

Cited by 168 publications

References 118 publications

Chemo-mechanical Coupling in the Transport Cycle of a Type II ABC Transporter

Chemo-mechanical Coupling in the Transport Cycle of a Type II ABC Transporter

Raising the Performance of the Tinker-HP Molecular Modeling Package [Article v1.0]

Scaling molecular dynamics beyond 100,000 processor cores for large‐scale biophysical simulations

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